The Effect of Sevelamer Carbonate on Serum Trimethylamine-n-Oxide (TMAO) Level in Patients With Chronic Kidney Disease (CKD) Stage 3b-4

CKD Stage 4 Clinical Trial

Official title:

The Effect of Sevelamer Carbonate on Serum Trimethylamine-n-Oxide (TMAO) Level in Patients With Chronic Kidney Disease (CKD) Stage 3b-4: a Protocol of a Randomized, Parallel, Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03596749
• Other study ID #: SIMON
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 1, 2018
• Est. completion date: July 1, 2019

Study information

• Verified date: August 2018
• Source: Nanfang Hospital of Southern Medical University
• Contact: Fan Fan Hou, M.D.,PhD
• Phone: 0086-20-61641591
• Email: ffhouguangzhou[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to investigate effects of sevelamer carbonate on reducing TMAO in stage 3b-4 CKD (pre-dialysis) patients. The study will also investigate the safety and tolerability of sevelamer carbonate in study population and the effects of sevelamer carbonate on serum p-cresyl sulfate, indoxyl sulfate, LDL-C and uric acid.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 80
• Est. completion date: July 1, 2019
• Est. primary completion date: May 1, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 1. Men or women, aged from 18 to 75 years old;

• 2. Provide informed consent prior to enrolling in the study;

• 3. Estimated glomerular filtration rate (eGFR) between 15-45 ml/min/1.73 m2 (calculated by CKD-EPI equation)

Exclusion Criteria:

• 1. Documented poorly controlled diabetes mellitus, poorly controlled hypertension, malignant tumour, or any clinically significant unstable medical condition;

• 2. Active dysphagia or swallowing disorder; or a predisposition to or current bowel obstruction, ileus, or severe gastrointestinal motility disorders including severe constipation;

• 3. Known hypersensitivity to sevelamer or any constituents of the study drug;

• 4. Unable to comply with the requirements of the study;

• 5. Hypophosphatemia (serum phosphorus level <0.87mmol/L);

• 6. Women who have a positive pregnancy test at enrollment or women who are breast-feeding;

• 7. Have been enrolled in other interventional study;

• 8. Received sevelamer or other intestinal adsorbents, or broad-spectrum antibiotic within one month prior to the screening period.

Related Conditions & MeSH terms

• CKD Stage 3b
• CKD Stage 4
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Sevelamer Carbonate
Sevelamer carbonate 1600mg (p.o. b.i.d) with meals

Locations

Country	Name	City	State
China	Renal Division, Nanfang Hospital,Southern Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Fan Fan Hou

Country where clinical trial is conducted

China, 

References & Publications (10)

GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet. 2017 Sep 16;390(10100):1211-1259. doi: 10.1016/S0140-6736(17)32154-2. — View Citation

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med. 2004 Sep 23;351(13):1296-305. Erratum in: N Engl J Med. 2008;18(4):4. — View Citation

Goto S, Yoshiya K, Kita T, Fujii H, Fukagawa M. Uremic toxins and oral adsorbents. Ther Apher Dial. 2011 Apr;15(2):132-4. doi: 10.1111/j.1744-9987.2010.00891.x. Epub 2011 Mar 8. Review. — View Citation

Koopen AM, Groen AK, Nieuwdorp M. Human microbiome as therapeutic intervention target to reduce cardiovascular disease risk. Curr Opin Lipidol. 2016 Dec;27(6):615-622. Review. — View Citation

Rastogi A. Sevelamer revisited: pleiotropic effects on endothelial and cardiovascular risk factors in chronic kidney disease and end-stage renal disease. Ther Adv Cardiovasc Dis. 2013 Dec;7(6):322-42. doi: 10.1177/1753944713513061. Review. — View Citation

Tang WH, Wang Z, Kennedy DJ, Wu Y, Buffa JA, Agatisa-Boyle B, Li XS, Levison BS, Hazen SL. Gut microbiota-dependent trimethylamine N-oxide (TMAO) pathway contributes to both development of renal insufficiency and mortality risk in chronic kidney disease. Circ Res. 2015 Jan 30;116(3):448-55. doi: 10.1161/CIRCRESAHA.116.305360. Epub 2014 Nov 5. — View Citation

Vlassara H, Uribarri J, Cai W, Goodman S, Pyzik R, Post J, Grosjean F, Woodward M, Striker GE. Effects of sevelamer on HbA1c, inflammation, and advanced glycation end products in diabetic kidney disease. Clin J Am Soc Nephrol. 2012 Jun;7(6):934-42. doi: 10.2215/CJN.12891211. Epub 2012 Mar 29. — View Citation

Webster AC, Nagler EV, Morton RL, Masson P. Chronic Kidney Disease. Lancet. 2017 Mar 25;389(10075):1238-1252. doi: 10.1016/S0140-6736(16)32064-5. Epub 2016 Nov 23. Review. — View Citation

Yubero-Serrano EM, Woodward M, Poretsky L, Vlassara H, Striker GE; AGE-less Study Group. Effects of sevelamer carbonate on advanced glycation end products and antioxidant/pro-oxidant status in patients with diabetic kidney disease. Clin J Am Soc Nephrol. 2015 May 7;10(5):759-66. doi: 10.2215/CJN.07750814. Epub 2015 Feb 20. — View Citation

Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, Chen M, He Q, Liao Y, Yu X, Chen N, Zhang JE, Hu Z, Liu F, Hong D, Ma L, Liu H, Zhou X, Chen J, Pan L, Chen W, Wang W, Li X, Wang H. Prevalence of chronic kidney disease in China: a cross-sectional survey. Lancet. 2012 Mar 3;379(9818):815-22. doi: 10.1016/S0140-6736(12)60033-6. Erratum in: Lancet. 2012 Aug 18;380(9842):650. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in the serum concentration of TMAO between treatment group and control group	The serum concentration of TMAO will be evaluated by high performance liquid chromatography (HPLC)	22 weeks
Secondary	Difference in the serum concentration of p-cresyl sulfate between treatment group and control group	The serum concentration of p-cresyl sulfate will be evaluated by high performance liquid chromatography (HPLC)	22 weeks
Secondary	Difference in the serum concentration of indoxyl sulfate between treatment group and control group	The serum concentration of indoxyl sulfate will be evaluated by high performance liquid chromatography (HPLC)	22 weeks
Secondary	Difference in the serum concentration of LDL-C between treatment group and control group	Chemistry evaluations	22 weeks
Secondary	Difference in the serum concentration of uric acid between treatment group and control group	Chemistry evaluations	22 weeks